Estimating the potential cost of a high dose immune tolerance induction ( ITI ) therapy relative to the cost of a combined therapy of a low dose ITI therapy with bypassing agent prophylaxis

The International Immune Tolerance Study (I‐ ITI ) demonstrated comparable success rates between low ( FVIII 50 IU/kg/TIW) and high dose ( FVIII 200 IU/kg/day) regimens. While costlier, the high dose ITI regimen achieved shorter time‐to‐treatment success with fewer bleeding episodes compared to the low dose ITI regimen. Adding bypassing agent prophylaxis ( BAP ) to a low dose ITI regimen may reduce bleeding while still being less costly than high dose ITI . Aim and Methods An economic model was developed to compare high dose ITI to low dose ITI with BAP . All model inputs were derived from clinical trials. The I‐ ITI study indicated a median time to negative inhibitor titre of 4.6 and 9.2 months and average number of bleeds/patient of 4.2 and 9.9 for the high and low dose regimens respectively. Based on the BAP trials, aPCC (85 U/kg/ TIW ) and rFVII a (90 μg/kg/day) achieved a 62% and 45% reduction in bleeding frequency respectively. Cost analysis was from a US third party payer perspective and limited to drug costs. One‐way, two‐way and probabilistic sensitivity analyses were performed. Results Costs of low dose ITI with aPCC prophylaxis until negative inhibitor titre is achieved was 24.0% less compared to high dose ITI . Low dose ITI with rFVII a prophylaxis cost 46.5% more compared to high dose ITI . Model results were robust in the majority of the sensitivity analyses. Conclusion A low dose ITI regimen with aPCC prophylaxis may be cost saving compared to a high dose ITI regimen with the potential to reduce morbidity by lowering the risk for breakthrough bleeds.